Superior oxidase-mimetic activity of FeCo-NC dual-atom nanozyme for smartphone-based visually colorimetric assay of organophosphorus pesticides.

A colorimetric analysis platform has been successfully developed based on FeCo-NC dual-atom nanozyme (FeCo-NC DAzyme) for the detection of organophosphorus pesticides (OPPs). The FeCo-NC DAzyme exhibited exceptional oxidase-like activity (OXD), enabling the catalysis of colorless TMB to form blue oxidized TMB (oxTMB) without the need for H2O2 involvement. By combining acid phosphatase (ACP) hydrolase with FeCo-NC DAzyme, a "FeCo-NC DAzyme + TMB + ACP + SAP" colorimetric system was constructed, which facilitated the rapid detection of malathion. The chromogenic system was applied to detect malathion using a smartphone-based app and an auxiliary imaging interferogram device for colorimetric measurements, which have a linear range of 0.05-4.0 µM and a limit of detection (LOD) as low as 15 nM in real samples, comparable to UV-Vis and HPLC-DAD detection methods. Overall, these findings present a novel approach for convenient, rapid, and on-site monitoring of OPPs.

Increasing CRISPR/Cas9-mediated gene editing efficiency in T7 phage by reducing the escape rate based on insight into the survival mechanism.

Bacteriophages have been used across various fields, and the utilization of CRISPR/Cas-based genome editing technology can accelerate the research and applications of bacteriophages. However, some bacteriophages can escape from the cleavage of Cas protein, such as Cas9, and decrease the efficiency of genome editing. This study focuses on the bacteriophage T7, which is widely utilized but whose mechanism of evading the cleavage of CRISPR/Cas9 has not been elucidated. First, we test the escape rates of T7 phage at different cleavage sites, ranging from 10 -2 to 10 -5. The sequencing results show that DNA point mutations and microhomology-mediated end joining (MMEJ) at the target sites are the main causes. Next, we indicate the existence of the hotspot DNA region of MMEJ and successfully reduce MMEJ events by designing targeted sites that bypass the hotspot DNA region. Moreover, we also knock out the ATP-dependent DNA ligase 1. 3 gene, which may be involved in the MMEJ event, and the frequency of MMEJ at 4. 3 is reduced from 83% to 18%. Finally, the genome editing efficiency in T7 Δ 1. 3 increases from 20% to 100%. This study reveals the mechanism of T7 phage evasion from the cleavage of CRISPR/Cas9 and demonstrates that the special design of editing sites or the deletion of key gene 1. 3 can reduce MMEJ events and enhance gene editing efficiency. These findings will contribute to advancing CRISPR/Cas-based tools for efficient genome editing in phages and provide a theoretical foundation for the broader application of phages.

Distribution, source apportionment, and ecological risk assessment of soil antibiotic resistance genes in urban green spaces.

Urban green spaces play a crucial role in cities by providing near-natural environments that greatly impacts the health of residents. However, these green spaces have recently been scrutinized as potential reservoirs of antibiotic resistance genes (ARGs), posing significant ecological risks. Despite this concern, our understanding of the distribution, sources, and ecological risks associated with ARGs remains limited. In this study, we investigated the spatial distribution of soil ARGs using spatial interpolation and auto-correlation analysis. To apportion the source of soil ARGs in urban green spaces of Tianjin, Geo-detector method (GDM) was employed. Furthermore, we evaluated the ecological risk posed by ARGs employing risk quotients (RQ). The results of our study showed a significantly higher abundance of Quinolone resistance genes in the soil of urban green spaces in Tianjin. These genes were mainly found in the northwest, central, and eastern regions of the city. Our investigation identified three main factors contributing to the presence of soil ARGs: antibiotic production, precipitation, livestock breeding, and hospital. The results of ecological risk in RQ value showed a high risk associated with Quinolone resistance genes, followed by Aminoglycoside, Tetracycline, Multidrug, MLSB, Beta Lactam, Sulfonamide, and Chloramphenicol. Mantel-test and correlation analysis revealed that the ecological risk of ARGs was greatly influenced by soil properties and heavy metals. This study provides a new perspective on source apportionment and the ecological risk assessment of soil ARGs in urban green spaces.

Diagnostic performance of MRI for assessing axillary lymph node status after neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis.

OBJECTIVE: This systematic review examined the diagnostic performance of magnetic resonance imaging (MRI) for assessing axillary lymph node status (ALNS) after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies and used the QUADAS-2 tool to assess methodological quality of eligible studies. We used STATA version 12.0 to perform data pooling, heterogeneity testing, subgroup analysis, and sensitivity analysis. RESULTS: For the 21 enrolled studies, including 2875 patients, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were respectively 0.63 (95% CI: 0.53-0.72), 0.75 (95% CI: 0.68-0.81), 2.52 (95% CI: 1.98-3.19), 0.50 (95% CI: 0.39-0.63), and 5.08 (95% CI: 3.38-7.63). The AUC was 0.76 (95% CI: 0.72-0.79). I2 values of sensitivity (I2 = 94.41%) and specificity (I2 = 88.97%) were both > 50%. For the initial positive ALN patients, the pooled sensitivity and specificity were 0.64 (95% CI: 0.53-0.75) and 0.74 (95% CI: 0.64-0.82), respectively. Sensitivity analyses by focusing on studies with MRI performed post-NAC, studies using DCE-MRI, or studies with low risk of bias showed similar results to the primary analyses. CONCLUSION: MRI may have suboptimal diagnostic value in assessing ALNS after NAC for breast cancer patients. Due to the inconsistency of NAC regimens, the variability of axillary surgery, and the lack of time interval between MRI and surgery, further studies are needed to confirm our findings. CLINICAL RELEVANCE STATEMENT: Our study provided the diagnostic value of MRI in assessing axillary lymph node status after neoadjuvant chemotherapy for breast cancer patients. KEY POINTS: • MRI may have suboptimal diagnostic value in assessing axillary lymph node status after NAC for general breast cancer patients. • The initial axillary lymph node status has little impact on the diagnostic efficacy of MRI. • The substantial heterogeneity among studies highlights the need for further studies to provide more high-quality evidence in this field.

Ultrasound assisted wall-breaking extraction and primary structures, bioactivities, rheological properties of novel Exidia yadongensis polysaccharide.

New natural multifunctional polysaccharide and its innovatory extraction technology may be urgently needed for food industries. Our aims were to establish new extraction method and investigate the primary structures, bioactivities and rheological properties of novel E. yadongensis polysaccharide (EYP). Ultrasound assisted mechanical wall-breaking extraction (MAUE) was successfully established for the EYP extraction from a new E. yadongensis. Based on the MAUE with RSM, the polysaccharide yield of 17.92 ± 0.56 % with the optimal parameters of five extraction factors were obtained, and current MAUE was characterized by its high yield, low extraction temperature and short ultrasound time. After the isolation and purification, the EYP as a protein-bound polysaccharide was obtained. FT-IR and NMR analysis showed that the main backbone of the EYP comprised of (1 â†’ 4)-ß-D-glucopyranosyl and (1 â†’ 6)-ɑ-D-mannopyranosyl groups; EYP exhibited significant antioxidant, antibacterial, antitumor, antidiabetic activities, and good viscoelastic properties in low pH solutions (P < 0.05). The EYP may be used as a natural functional and cohesive agent in food industries.

MRI radiomics for the preoperative evaluation of lymphovascular invasion in breast cancer: A meta-analysis.

PURPOSE: To evaluate the ability of preoperative MRI-based radiomic features in predicting lymphovascular invasion (LVI) in patients with breast cancer. METHODS: PubMed, Embase, Web of Science, Cochrane Library databases, and four Chinese databases were searched to identify relevant studies published up until June 15, 2023. Two reviewers screened all papers independently for eligibility. We included diagnostic accuracy studies that used radiomics-MRI for LVI in patients with breast cancer, using histopathology as the reference standard. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 and Radiomics Quality Score. Overall diagnostic odds ratio (DOR), sensitivity, specificity and area under the curve (AUC) were calculated to assess the prediction efficacy of MRI-based radiomic features in patients with breast cancer. Spearman's correlation coefficient was calculated and subgroup analysis performed to investigate causes of heterogeneity. RESULTS: Eight studies comprising 1685 female patients were included. The pooled DOR, sensitivity, specificity, and AUC of radiomics in detecting LVI were 23 [confidence interval (CI) 16,32], 0.89(0.86,0.92), 0.82 (0.78,0.86), and 0.83(0.78,0.87), respectively. The meta-analysis showed significant heterogeneity among the included studies. No threshold effect was detected. Subgroup analysis showed that more than 200 participants, radiomics with clinical factors, semiautomatic segmentation method and peritumoral or intra- and peritumoral model [DOR: 28(18,42), 26(19,37), 34(16,70), 40(10,156), respectively] could improve diagnostic performance compared with less than 200 participants, only radiomics, manual segmentation method, and tumor model [DOR: 16(7,37), 21(6,73), 20(12,32), 21(13,32), respectively], but 3.0 T MR and multiple sequences approach [DOR: 27(15,49),17(8,35)] couldn't improve diagnostic performance compared with 1.5 T and DCE radiomic features [DOR:27(7,99),25(17,37)]. CONCLUSION: Our meta-analysis showed that preoperative MRI-based radiomic features performs well in predicting LVI in patients with breast cancer. This noninvasive and convenient tool may be used to facilitate preoperative identification of LVI in breast cancer.

Different Imaging Modalities for the Diagnosis of Axillary Lymph Node Metastases in Breast Cancer: A Systematic Review and Network Meta-Analysis of Diagnostic Test Accuracy.

BACKGROUND: Accurate diagnosis of axillary lymph node metastasis (ALNM) of breast cancer patients is important to guide local and systemic treatment. PURPOSE: To evaluate the diagnostic performance of different imaging modalities for ALNM in patients with breast cancer. STUDY TYPE: Systematic review and network meta-analysis (NMA). SUBJECTS: Sixty-one original articles with 8011 participants. FIELD STRENGTH: 1.5 T and 3.0 T. ASSESSMENT: We used the QUADAS-2 and QUADAS-C tools to assess the risk of bias in eligible studies. The identified articles assessed ultrasonography (US), MRI, mammography, ultrasound elastography (UE), PET, CT, PET/CT, scintimammography, and PET/MRI. STATISTICAL ANALYSIS: We used random-effects conventional meta-analyses and Bayesian network meta-analyses for data analyses. We used sensitivity and specificity, relative sensitivity and specificity, superiority index, and summary receiver operating characteristic curve (SROC) analysis to compare the diagnostic value of different imaging modalities. RESULTS: Sixty-one studies evaluated nine imaging modalities. At patient level, sensitivities of the nine imaging modalities ranged from 0.27 to 0.84 and specificities ranged from 0.84 to 0.95. Patient-based NMA showed that UE had the highest superiority index (5.95) with the highest relative sensitivity of 1.13 (95% confidence interval [CI]: 0.93-1.29) among all imaging methods when compared to US. At lymph node level, MRI had the highest superiority index (6.91) with highest relative sensitivity of 1.13 (95% CI: 1.01-1.23) and highest relative specificity of 1.11 (95% CI: 0.95-1.23) among all imaging methods when compared to US. SROCs also showed that UE and MRI had the largest area under the curve (AUC) at patient level and lymph node level of 0.92 and 0.94, respectively. DATA CONCLUSION: UE and MRI may be superior to other imaging modalities in the diagnosis of ALNM in breast cancer patients at the patient level and the lymph node level, respectively. Further studies are needed to provide high-quality evidence to validate our findings. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Stellate ganglion block relieves acute lung injury induced by severe acute pancreatitis via the miR-155-5p/SOCS5/JAK2/STAT3 axis.

Acute lung injury (ALI), a prevalent complication of severe acute pancreatitis (SAP), is also a leading contributor to respiratory failure and even death of SAP patients. Here, we intended to investigate the function and mechanism of stellate ganglion block (SGB) in ameliorating SAP-induced ALI (SAP-ALI). We engineered an SAP-ALI model in rats and treated them with SGB. HE staining and the dry and wet method were implemented to evaluate pathological alterations in the tissues and pulmonary edema. The rats serum changes of the profiles of TNF-α, IL-6, IL-1ß, and IL-10 were examined. The profiles of miR-155-5p and SOCS5/JAK2/STAT3 were detected. Functional assays were performed for confirming the role of miR-155-5p in modulating the SOCS5/JAK2/STAT3 pathway in pulmonary epithelial cells. Our findings revealed that SGB vigorously alleviated SAP rat lung tissue damage and lung edema and lessened the generation of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß. SGB enhanced SOCS5 expression, hampered miR-155-5p, and suppressed JAK2/STAT3 pathway activation. As evidenced by mechanism studies, miR-155-5p targeted the 3'UTR of SOCS5 and repressed its expression, hence resulting in JAK2/STAT3 pathway activation. During animal trials, we discovered that SGB ameliorated SAP-ALI, boosted SOCS5 expression, and mitigated the levels of pro-inflammatory factors and miR-155-5p in the plasma. In vitro, miR-155-5p overexpression substantially facilitated pulmonary epithelial cell apoptosis, inflammation, and JAK2/STAT3 pathway activation and restrained SOCS5 expression. All in all, our work hinted that SGB could modulate the miR-155-5p/SOCS5/JAK2/STAT3 axis to alleviate SAP-ALI.

A turn-off Eu-MOF@Fe2+ sensor for the selective and sensitive fluorescence detection of bromate in wheat flour.

A new europium metal-organic framework (Eu-MOF) was prepared by simple hydrothermal method. The product exhibited intense red fluorescence, long fluorescence lifetime (0.454 ms) and excellent fluorescence stability. The fluorescence titration result showed that Fe3+ could completely quench the fluorescence of Eu-MOF, while the fluorescence quenching effect of Fe2+ or bromate was negligible. Considering the strong oxidizing property of bromate, a "turn off" Eu-MOF@Fe2+ sensor toward bromate was designed by generating Fe3+ due to the redox reaction. The results showed that the sensor displayed a wide linear range (0-0.2 mM), high sensitivity (LOD = 3.7 × 10-6 mol/L), good selectivity and resistant to possible interferences in real four sample. Furthermore, the detection mechanism was investigated by PXRD, XPS and UV-Vis methods. More importantly, the Eu-MOF@Fe2+ sensor was further applied to detect bromate in wheat flour with satisfactory recovery (95.30%-104.38%) and accuracy (RSD < 2.85%). These results suggest that Eu-MOF@Fe2+ can be used as a potential sensor to detect bromate in food industry.

Calreticulin silencing inhibits extracellular matrix synthesis of human gingival fibroblasts cultured on three-dimensional poly(lactic-co-glycolic acid) scaffolds by inhibiting the calcineurin/nuclear factor of activated T cells 3 signalling pathway.

BACKGROUND: The retraction and compression of gingival tissue have a significant impact on the efficiency and stability of orthodontic treatment, but the underlying molecular mechanism has not been fully elucidated. The aim of the current study was to investigate the effects of mechanical forces on the expression level of calreticulin (CRT), the activity of the calcineurin (CaN)/nuclear factor of activated T cells (NFAT) 3 signalling pathway, and extracellular matrix (ECM) synthesis in human gingival fibroblasts (HGFs) cultured on three-dimensional (3D) poly(lactic-co-glycolic acid) (PLGA) scaffolds and to further explore the mechanical transduction pathways that may be involved. MATERIALS AND METHODS: A mechanical force of 25 g/cm2 was applied to HGFs for 0, 6, 24, 48, or 72 h. The expression of CRT, CaN, NFAT3, phosphorylated NFAT3 (p-NFAT3) and type I collagen (COL-I) were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Subsequently, small interfering RNA (siRNA) was used to knock down the expression of CRT in HGFs, and the impacts of the applied force on the expression levels of CaN, NFAT3, p-NFAT3, and COL-I were also evaluated by RT-qPCR and western blotting. RESULTS: The application of mechanical force on HGFs cultured on 3D PLGA scaffolds led to a significant increases in CRT, CaN, and COL-I expression as well as a decrease in p-NFAT3 expression. However, the effects of mechanical force on CaN, p-NFAT3, and COL-I expression were reversed following downregulation of CRT and displayed a significant decrease in CaN/NFAT3 activity and COL-I synthesis. CONCLUSION: This study showed that the CaN/NFAT3 signalling pathway and CRT appear to be involved in the mechanotransduction of HGFs, and downregulation of CRT inhibits COL-I synthesis potentially via the CaN/NFAT3 signalling pathway. Taken together, these findings ultimately provide novel insight into the mechanisms underlying mechanical force-induced ECM synthesis, which may be conducive to the development of targeted therapeutics to treat fibrotic diseases, including gingival fibrosis caused by orthodontic treatment.

[Establishment of Quantitative SPR Assay for Antibodies Against Human Platelet Antigen-1a].

OBJECTIVE: To establish quantitative surface plasmon resonance (SPR) assay for antibodies against human platelet antigen-1a (HPA-1a). METHODS: Recombinant protein was fixed on the chip surface by amino coupling method. SPR assay was used to detect the standard antibodies against HPA-1a at different conceatration. The optimal experimental parameters were determined, and standard curves were constructed with linear regression. Moreover, the sensitivity, specificity, accuracy and precision of the assay were evaluated. RESULTS: The quantitative SPR assay for HPA-1a antibodies was established. The determination ranges were 0-20 IU, with accuracy (recovery rate) was 97.75%-103.08%. The intra-assay precision [coefficients of variation (CV)] was 3.53%-4.29%, and the inter-assay precision (CV) was 2.08%-4.40%. For specificity test, several kinds of monoclonal and human antibodies against platelet membrane protein were tested and no positive result was observed. CONCLUSION: The established quantitative SPR assay for HPA-1a antibodies shows good sensitivity, specificity, accuracy and precision, and this rapid and simple method provides a new reference method for scientific research and clinical antibody detection.

Optimization of T4 phage engineering via CRISPR/Cas9.

A major limitation hindering the widespread use of synthetic phages in medical and industrial settings is the lack of an efficient phage-engineering platform. Classical T4 phage engineering and several newly proposed methods are often inefficient and time consuming and consequently, only able to produce an inconsistent range of genomic editing rates between 0.03-3%. Here, we review and present new understandings of the CRISPR/Cas9 assisted genome engineering technique that significantly improves the genomic editing rate of T4 phages. Our results indicate that crRNAs selection is a major rate limiting factor in T4 phage engineering via CRISPR/Cas9. We were able to achieve an editing rate of > 99% for multiple genes that functionalizes the phages for further applications. We envision that this improved phage-engineering platform will accelerate the fields of individualized phage therapy, biocontrol, and rapid diagnostics.

Blood group-related antigen Ley on human platelets and its involvement in platelet aggregation via a possible interaction with CD61.

BACKGROUND: The Ley antigen is a carbohydrate chain belonging to the ABH-Lewis blood group family. Ley has been reported to be present on red blood cells (RBCs) and granulocytes, but its distribution and function in platelets remain unknown. There are a variety of glycoproteins on platelets, which may carry the Ley antigen. This study aims to investigate the expression pattern and the function of Ley in human platelets. STUDY DESIGN AND METHODS: Flow cytometry, Western blot, and immunofluorescence assays were performed to determine Ley expression on human platelets. ADP (1.25-10 µM) and thrombin (0.05-1 IU/mL) were used to activate platelets in the presence or absence of prostaglandin E1 (PGE1) and the Ley expression was evaluated again by flow cytometry. Blockade was performed with an anti-Ley monoclonal antibody to verify the role of this epitope in platelet function. Finally, coimmunoprecipitation was performed to identify glycoproteins associated with Ley . RESULTS: Ley was expressed on human platelets independent of ABO blood type. Ley expression was decreased in a dose-dependent manner after activation with either ADP or thrombin, and this effect could be partially reversed by PGE1. Anti- Ley mAb treatment increased alpha-granule release and neutralized the inhibitory effect of the anti-CD61 antibody on platelet aggregation. In addition, Ley was proven to interact and colocalize with CD61. CONCLUSIONS: These results demonstrate nondifferential expression of Ley in platelets of different ABO blood types and suggest the involvement of Ley in platelet function, possibly via interaction with CD61.

Comparative Effectiveness of Different Combinations of Treatment Interventions in Patients with Stroke at the Convalescence Stage Based on the Markov Decision Process.

OBJECTIVE: The objective of this study was to compare the effectiveness of different combinations of interventions in patients with stroke at the convalescence stage based on the electronic health records (EHRs) by using the Markov decision process (MDP) theory and explore the feasibility of the Markov model in the real-world study (RWS). METHODS: Screening was conducted for patients with stroke at the convalescence stage who were admitted to the Third Affiliated Hospital of Zhejiang Chinese Medical University from January 2012 to January 2017 based on the EHRs. The relevant clinical data were extracted, and the appropriate conversion was made (state-action-reward) according to the Markov model. The transformed data were analysed and solved by the MDP to obtain the best interventions for patients with various stroke recovery periods. RESULTS: 926 patients with stroke at the convalescence stage were initially selected. And according to the inclusion exclusion criteria, 854 patients were screened. Through the MDP, we obtained the following results: (1)when the patients with stroke at the convalescence stage have a medical history, but no complications, and mild neurological impairment, ≥66-year- and 18-45-year-old patients are advised to choose acupuncture treatment. 46-65-year-old patients are advised to choose rehabilitation treatment. When patients with moderate to severe neurological impairment, patients are advised to choose rehabilitation, Chinese herbal decoction, and acupuncture combined therapy. (2) Without complications or medical history, patients who are ≥ 66 years old are recommended to choose rehabilitation treatment when the nerve function impairment is mild; rehabilitation and acupuncture treatment are recommended when moderate and severe injuries are caused. (3) The combination of rehabilitation, Chinese herbal decoction, and acupuncture treatment is recommended for patients with phlegm and blood stasis. Acupuncture treatment is recommended for patients with mild impairment of nerve function in qi deficiency and blood stasis type. Rehabilitation, Chinese herbal decoction, and acupuncture treatment are recommended for moderate-severe injuries. CONCLUSIONS: The MDP makes it possible to study the effectiveness of various treatment methods in stroke patients who are at the convalescence stage. Further exploratory studies using MDP theory in other areas in which complex interventions are common would be worthwhile.

Enhancement of long-lived luminescence in nanophosphors by surface defect passivation.

Herein, we found that surface defects quench persistent luminescence in nanophosphors. Passivation of surface defects by thermal treatment or surface coating can effectively enhance the intensity and prolong the decay time of persistent luminescence. The surface passivated persistent nanophosphors are promising in autofluorescence-free bioimaging and time-gated steganography.

Preparation of porous materials by selective enzymatic degradation: effect of in vitro degradation and in vivo compatibility.

Poly(butylene succinate) (PBS) and poly(lactic acid) (PLA) were melt-blended and formed into a film by hot press forming. The film was selectively degraded by cutinase and proteinase K to form a porous material. The porous materials were characterized with respect to their pore morphology, pore size, porosity and hydrophilicity. The porous materials were investigated in vitro degradation and in vivo compatibility. The results show that the pore size of the prepared porous materials could be controlled by the proportion of PBS and the degradation time. When the PBS composition of PBS/PLA blends was changed from 40 wt% to 50 wt%, the mean pore diameter of the porous materials significantly increased from 6.91 µm to 120 µm, the porosity improved from 81.52% to 96.90%, and the contact angle decreased from 81.08° to 46.56°. In vitro degradation suggests that the PBS-based porous materials have a good corrosion resistance but the PLA-based porous materials have degradability in simulated body fluid. Subcutaneous implantation of the porous materials did not cause intense inflammatory response, which revealed good compatibility. The results of hematoxylin and eosin and Masson's trichrome staining assays demonstrated that the porous materials promote chondrocyte production. Porous materials have great potential in preparing implants for tissue engineering applications.

Serum interleukin-33 as a novel marker for long-term prognosis and recurrence in acute ischemic stroke patients.

OBJECTIVES: Interleukin-33, a newly identified member of interleukin-1 family, had been confirmed to play a crucial role in regulating inflammatory responses in various disease. However, the exact role of interleukin-33 in the disease process of acute ischemic stroke still remains unclear. This study aims to demonstrate the relationship between interleukin-33 levels and long-term functional outcome as well as ischemic stroke recurrence. METHODS: Three hundred and four first-ever acute ischemic stroke patients were recruited and basic information and history of all subjects taken within 72 hr on admission. The functional outcome was estimated by Barthel index. The multivariate logistic regression was used to analyze the prognosis, while the Cox proportional hazard model was applied to assess the recurrence risk. RESULTS: Out of 304 subjects, 259 patients successfully completed scheduled two-year follow-up. We found that higher interleukin-33 levels correlated positively with better prognosis as compared with those with lower interleukin-33 levels who presented with poorer outcome (62.45 ± 20.50 ng/ml vs. 51.58 ± 19.16 ng/ml, p < .001). After adjustment of all confounders, interleukin-33 was associated with the one-year prognosis with an adjusted odds ratio of 0.956 (95% confidence interval, 0.937-0.976, p < .001). Furthermore, interleukin-33 levels were also closely related to recurrent ischemic stroke with an adjusted hazard ratio of 0.979 (95% confidence interval, 0.961-0.997, p = .025). CONCLUSIONS: IL-33 can be used to predict the long-term outcomes and ischemic stroke recurrence in first-ever acute ischemic stroke patients.

Recent Progress in Time-Resolved Biosensing and Bioimaging Based on Lanthanide-Doped Nanoparticles.

Luminescent nanomaterials have attracted great attention in luminescence-based bioanalysis due to their abundant optical and tunable surface physicochemical properties. However, luminescent nanomaterials often suffer from serious autofluorescence and light scattering interference when applied to complex biological samples. Time-resolved luminescence methodology can efficiently eliminate autofluorescence and light scattering interference by collecting the luminescence signal of a long-lived probe after the background signals decays completely. Lanthanides have a unique [Xe]4fN electronic configuration and ladder-like energy states, which endow lanthanide-doped nanoparticles with many desirable optical properties, such as long luminescence lifetimes, large Stokes/anti-Stokes shifts, and sharp emission bands. Due to their long luminescence lifetimes, lanthanide-doped nanoparticles are widely used for high-sensitive biosensing and high-contrast bioimaging via time-resolved luminescence methodology. In this review, recent progress in the development of lanthanide-doped nanoparticles and their application in time-resolved biosensing and bioimaging are summarized. At the end of this review, the current challenges and perspectives of lanthanide-doped nanoparticles for time-resolved bioapplications are discussed.

Dual-Aptamer-Conjugated Molecular Modulator for Detecting Bioactive Metal Ions and Inhibiting Metal-Mediated Protein Aggregation.

Bioactive metal ions play important roles in both physiological and pathological processes. Developing biosensing probes for bioactive metal ion detection can contribute to fields including disease diagnosis and therapy and studying the mechanisms of biological activities. In this work, we designed a dual-aptamer-conjugated molecular modulator that can detect Zn2+ and further inhibit Zn2+-induced amyloid ß (Aß) aggregation. The molecular modulator is able to selectively target Aß species and block Zn2+ due to the specific recognition capability of aptamers. With the binding of Zn2+, the fluorescence signal of this molecular modulator is restored, thus allowing for Zn2+ detection. More importantly, this molecular modulator can inhibit the generation of Zn2+-triggered Aß aggregates due to the trapping of Zn2+ around Aß species. Circular dichroism measurements reveal that the dual-aptamer-conjugated molecular modulator prevents the conformational transition of the Aß monomer from a random coil to a ß-sheet. Furthermore, after treating with the molecular modulator, no Aß aggregate is observed in the Aß solution with added Zn2+, demonstrating that Aß aggregation is successfully inhibited by this molecular modulator. Our approach provides a promising tool for detecting bioactive metal ions and studying the molecular mechanisms behind life activities.